tbuckley/cabot-search huggingface dataset:
Changes in survival in de novo metastatic cancer in an era of new medicines
Authors: Marianne Luyendijk, Otto Visser, Hedwig M Blommestein, Ignace H J T de Hingh, Frank J P Hoebers, Agnes Jager, Gabe S Sonke, Elisabeth G E de Vries, Carin A Uyl-de Groot, Sabine Siesling
Journal: JNCI Journal of the National Cancer Institute (2023)

Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years.For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989-1993 and 2014-2018.Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0-50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer.Over 30 years, the survival of patients with de novo M1 disease modestly and unevenly increased among cancers. Metastatic cancer still remains a very lethal disease. Next to better treatment options, we call for better preventive measures and early detection to reduce the incidence of metastatic disease.
The stunning clodronate
Authors: Elvira Mass
Journal: The Journal of Experimental Medicine (2023)

Not only macrophages, but also neutrophils, are a main target of clodronate. In this issue of JEM, Culemann et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20220525) demonstrate that anti-inflammatory effects of clodronate liposomes are driven via stunning of polymorphonuclear neutrophils and not solely through depletion of macrophages.
At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study
Authors: Julia Wigren Byström, Linnea Vikström, Ebba Rosendal, Remigius Gröning, Yong-Dae Gwon, Emma Nilsson, Atin Sharma, Akbar Espaillat, Leo Hanke, Gerald McInerney, Andrea Puhar, Felipe Cava, Gunilla B Karlsson Hedestam, Therese Thunberg, Tor Monsen, Fredrik Elgh, Magnus Evander, Anders F Johansson, Anna K Överby, Clas Ahlm, Johan Normark, Mattias NE Forsell
Journal: Eurosurveillance (2023)

BackgroundThe current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.AimThe aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.MethodsWe developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.ResultsWe demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.ConclusionImplementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.
Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes
Authors: Stephan Culemann, Katharina Knab, Maximilien Euler, Anja Wegner, Hilal Garibagaoglu, Jochen Ackermann, Kim Fischer, Deborah Kienhöfer, Georgiana Crainiciuc, Jonas Hahn, Anika Grüneboom, Falk Nimmerjahn, Stefan Uderhardt, Andrés Hidalgo, Georg Schett, Markus H. Hoffmann, Gerhard Krönke
Journal: The Journal of Experimental Medicine (2023)

Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.
A review of genotrichoses and hair pathology associated with inherited skin diseases
Authors: Brent J Doolan, Tuntas Rayinda, Frank P Chiu, John A McGrath, Alexandros  Onoufriadis
Journal: British Journal of Dermatology (2023)

Abstract Genetic hair disorders, also known as genotrichoses, are characterized by abnormalities of hair structure, growth or differentiation, giving rise to a spectrum of phenotypes such as hypertrichosis, hypotrichosis and atrichia. These disorders may present as isolated phenotypes or be part of more complex phenotypes including abnormalities in skin or other organs. Genetic discoveries for hair disorders have been recently augmented with the advent of next-generation sequencing (NGS) technologies. We reviewed the literature and summarized disease–gene associations for inherited hair disorders, as well as genodermatoses presenting with hair abnormalities discovered by NGS technologies. We identified 28 nonsyndromic hair disorders, involving 25 individual genes and four unidentified genes. We have also discovered that approximately 30% of all the genodermatoses that were identified by NGS approaches demonstrated hair abnormalities as part of their phenotype. This review underscores the huge impact of NGS technologies in disclosing the genetics of hair disorders and the potential these discoveries provide for future translational research and new therapies.
Risk of SARS-CoV-2 reinfection by vaccination status, predominant variant and time from prior infection: a cohort study, Reggio Emilia province, Italy, February 2020 to February 2022
Authors: Massimo Vicentini, Francesco Venturelli, Pamela Mancuso, Eufemia Bisaccia, Alessandro Zerbini, Marco Massari, Andrea Cossarizza, Sara De Biasi, Patrizio Pezzotti, Emanuela Bedeschi, Paolo Giorgi Rossi
Journal: Eurosurveillance (2023)

BackgroundUnderstanding the epidemiology of reinfections is crucial for SARS-CoV-2 control over a long period.AimTo evaluate the risk of SARS-CoV-2 reinfection by vaccination status, predominant variant and time after first infection.MethodsWe conducted a cohort study including all residents in the Reggio Emilia province on 31 December 2019, followed up until 28 February 2022 for SARS-CoV-2 first infection and reinfection after 90 days. Cox models were used to compare risk of first infection vs reinfection, adjusting for age, sex, vaccine doses and comorbidities.ResultsThe cohort included 538,516 residents, 121,154 with first SARS-CoV-2 infections and 3,739 reinfections, most in the Omicron BA.1 period. In the pre-Omicron period, three doses of vaccine reduced risk of reinfection by 89% (95% CI: 87-90), prior infection reduced risk by 90% (95% CI: 88-91), while two doses and infection reduced risk by 98% (95% CI: 96-99). In the Omicron BA.1 period, protection estimates were 53% (95% CI: 52-55), 9% (95% CI: 4-14) and 76% (95% CI: 74-77). Before Omicron, protection from reinfection remained above 80% for up to 15 months; with Omicron BA.1, protection decreased from 71% (95% CI: 65-76) at 5 months to 21% (95% CI: 10-30) at 22 months from the first infection. Omicron BA.1 reinfections showed 48% (95% CI: 10-57) lower risk of severe disease than first infections.ConclusionsNatural immunity acquired with previous variants showed low protection against Omicron BA.1. Combined vaccination and natural immunity seems to be more protective against reinfection than either alone. Vaccination of people with prior infection reduced the risk of severe disease.
Flashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast Cancer
Authors: Clifford A. Hudis
Journal: Journal of Clinical Oncology (2023)

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. March 29, 2023 Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. March 29, 2023 ARTICLE CITATION DOI: 10.1200/JCO.22.02784 Journal of Clinical Oncology - published online before print March 29, 2023 PMID: 36989608 Flashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast Cancer Clifford A. Hudis , MD1,2xClifford A. HudisSearch for articles by this author Show More 1Former Associate Editor, Journal of Clinical Oncology, Alexandria, VA2American Society of Clinical Oncology, Alexandria, VA https://doi.org/10.1200/JCO.22.02784 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn 1998, with the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18, Fisher et al1 demonstrated that preoperative (earlier) use of conventional postoperative adjuvant therapy did not improve or diminish overall outcomes (disease-free and overall survival) in early-stage breast cancer. In 2008, Liedtke et al2 suggested that response (specifically failure to achieve a pathologic complete response) after preoperative therapy could identify those patients with poor prognosis triple-negative disease who would have worse long-term outcomes. The impact of these studies today is that we can offer preoperative therapy where it is needed knowing it is safe and effective, and we can use this setting to help accelerate the pace of research.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast CancerThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Clifford A. HudisUncompensated Relationships: Alliance Foundation Trials, Columbia University, Memorial Sloan-Kettering Cancer CenterOpen Payments Link: https://openpaymentsdata.cms.gov/physician/471974No other potential conflicts of interest were reported. Companion Effect of preoperative chemotherapy on the outcome of women with operable breast cancer Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
The unique neuropathological vulnerability of the human brain to aging
Authors: Ferrer I
Journal: Ageing Research Reviews (2023)

Alzheimer's disease (AD)-related neurofibrillary tangles (NFT), argyrophilic grain disease (AGD), aging-related tau astrogliopathy (ARTAG), limbic predominant TDP-43 proteinopathy (LATE), and amygdala-predominant Lewy body disease (LBD) are proteinopathies that, together with hippocampal sclerosis, progressively appear in the elderly affecting from 50% to 99% of individuals aged 80 years, depending on the disease. These disorders usually converge on the same subject and associate with additive cognitive impairment. Abnormal Tau, TDP-43, and α-synuclein pathologies progress following a pattern consistent with an active cell-to-cell transmission and abnormal protein processing in the host cell. However, cell vulnerability and transmission pathways are specific for each disorder, albeit abnormal proteins may co-localize in particular neurons. All these alterations are unique or highly prevalent in humans. They all affect, at first, the archicortex and paleocortex to extend at later stages to the neocortex and other regions of the telencephalon. These observations show that the phylogenetically oldest areas of the human cerebral cortex and amygdala are not designed to cope with the lifespan of actual humans. New strategies aimed at reducing the functional overload of the human telencephalon, including optimization of dream repair mechanisms and implementation of artificial circuit devices to surrogate specific brain functions, appear promising.
Clonal hematopoiesis detection in patients with cancer using cell-free DNA sequencing
Authors: Lauren Fairchild, Jeanne Whalen, Katie D’Aco, Jincheng Wu, Carroll B. Gustafson, Nadia Solovieff, Fei Su, Rebecca J. Leary, Catarina D. Campbell, O. Alejandro Balbin
Journal: Science Translational Medicine (2023)

In the context of cancer, clonal hematopoiesis of indeterminate potential (CHIP) is associated with the development of therapy-related myeloid neoplasms and shorter overall survival. Cell-free DNA (cfDNA) sequencing is becoming widely adopted for genomic screening of patients with cancer but has not been used extensively to determine CHIP status because of a requirement for matched blood and tumor sequencing. We present an accurate classification approach to determine the CH status from cfDNA sequencing alone, applying our model to 4324 oncology clinical cfDNA samples. Using this method, we determined that 30.3% of patients in this cohort have evidence of CH, and the incidence of CH varies by tumor type. Matched RNA sequencing data show evidence of increased inflammation, especially neutrophil activation, within the tumors and tumor microenvironments of patients with CH. In addition, patients with CH had evidence of neutrophil activation systemically, pointing to a potential mechanism of action for the worse outcomes associated with CH status. Neutrophil activation may be one of many mechanisms, however, because patients with estrogen receptor–positive breast cancer harboring TET2 frameshift mutations had worse outcomes but similar neutrophil frequencies to patients without CH. Together, these data show the feasibility of detecting CH through cfDNA sequencing alone and an application of this method, demonstrating increased inflammation in patients with CH both systemically and in the tumor microenvironment.
A methodological approach to intra-action reviews - application and adaptation of existing global guidance during the COVID-19 pandemic response in Ireland, 2021
Authors: Eoghan O’Connor, Mary O’Riordan, Mary C. Morrissey, Niamh Dever, Cliodhna O’Mahony, Shem Romanowski, Máirín Boland
Journal: Eurosurveillance (2023)

Many countries were under-prepared for the arrival of an emergency such as the COVID-19 pandemic. An intra-action review allows countries, systems and services to reflect on their preparedness and response to date, and revise their policies and approaches as needed. We describe the approach to undertaking an intra-action review of Ireland’s Health Protection COVID-19 response during 2021. A project team within National Health Protection developed a project plan, identified key stakeholders, trained facilitators and designed workshop programmes, employing integrated collaborative web tools. Multidisciplinary representatives participated in three half-day, independently facilitated workshops on challenges and solutions within specific response areas: communication, governance and cross-cutting themes such as staff well-being. An all-stakeholder survey sought further in-depth detail. Participants reviewed the ongoing pandemic response in terms of good practice and challenges and recommended implementable solutions. We customised our mixed-methods approach using existing ECDC/WHO guidance, producing consensus recommendations during Ireland’s fourth wave of COVID-19, with particular focus on pathways to implementation. Our adaptations may help others in formulating and customising methodological approaches. During an emergency, identifying and reflecting on good practices to retain, and areas for strengthening, with a clear action plan of implementing recommendations, will enhance preparedness now, and for future emergencies.
Zwitterionic peptides: Tunable next-generation stealth nanoparticle modifications
Authors: Clyde Overby, Soomin Park, Austin Summers, Danielle S.W. Benoit
Journal: Bioactive Materials (2023)

Adsorption of proteins to nanoparticles (NPs), a complex process that results in a protein corona, is controlled by NP surface properties that define NP interactions in vivo. Efforts to control adsorbed protein quantity through surface modification have led to improvements in circulation time or biodistribution. Still, current approaches have yet to be identified to control adsorbed protein identities within the corona. Here, we report the development and characterization of diverse zwitterionic peptides (ZIPs) for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP sequence. Through serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona, we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence (charge motif). These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological function. Furthermore, overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.
Altered striatal actin dynamics drives behavioral inflexibility in a mouse model of fragile X syndrome
Authors: Valentina Mercaldo, Barbora Vidimova, Denise Gastaldo, Esperanza Fernández, Adrian C. Lo, Giulia Cencelli, Giorgia Pedini, Silvia De Rubeis, Francesco Longo, Eric Klann, August B. Smit, Seth G.N. Grant, Tilmann Achsel, Claudia Bagni
Journal: Neuron (2023)
Relation between Directly Detected Patent Foramen Ovale and Ischemic Brain Lesions in Sport Divers
Authors: Markus Schwerzmann, Christian Seiler, Ernst Lipp, Raphael Guzman, Karl O. Lövblad, Martin Kraus, Nils Kucher
Journal: Annals of Internal Medicine (2001)

Background: In divers, the significance of a patent foramen ovale and its potential relation to paradoxical gas emboli remain uncertain. Objective: To assess the prevalence of symptoms of decompression illness and ischemic brain lesions in divers with regard to the presence of a patent foramen ovale. Design: Retrospective cohort study. Setting: University hospital and three diving clubs in Switzerland. Participants: 52 sport divers and 52 nondiving controls. Measurements: Prevalence of self-reported decompression events, patent foramen ovale on contrast transesophageal echo-cardiography, and ischemic brain lesions on magnetic resonance imaging. Results: The risk for decompression illness events was 4.5-fold greater in divers with patent foramen ovale than in divers without patent foramen ovale (risk ratio, 4.5 [95% CI, 1.2 to 18.0]; P = 0.03). Among divers, 1.23 ± 2.0 and 0.64 ± 1.22 ischemic brain lesions per person (mean ± SD) were detected in those with and those without patent foramen ovale, respectively. Among controls, 0.22 ± 0.44 and 0.12 ± 0.63 lesion per person were detected (P < 0.001 for all groups). Conclusions: Regardless of whether a diver has a patent foramen ovale, diving is associated with ischemic brain lesions.
Phenylketonuria: Epitome of Human Biochemical Genetics
Authors: Charles R. Scriver, Carol L. Clow
Journal: New England Journal of Medicine (1980)

IN the half century since Følling's original description, 1 phenylketonuria (PKU) has become a classic example of a genetic disorder because it illustrates three historic principles of human and medical genetics.2 First of all, the disease is inherited as an autosomal-recessive trait according to Mendel's law of segregation, and it is listed (as entry 26160) in the modern catalogs of Mendelian Inheritance in Man. 3 Secondly, PKU is an "inborn error of metabolism," and it illustrates Garrod's cardinal principle of gene action: genetic factors specify chemical reactions and human biochemical individuality.4 The extensive clinical and biochemical heterogeneity of the hyperphenylalaninemias of . . .
A Prospective Study of Cigarette Smoking and Age-Related Macular Degeneration in Women
Authors: Johanna M. Seddon
Journal: JAMA (1996)

<h3>objective.</h3> —To evaluate the relationship between cigarette smoking and incidence of age-related macular degeneration (AMD) among women. <h3>Design.</h3> —Prospective cohort study with 12 years of follow-up (1980 to 1992), in which information on smoking habits was updated every 2 years. <h3>Setting.</h3> —Eleven states throughout the United States. <h3>Participants.</h3> —A total of 31 843 registered nurses enrolled in the Nurses' Health Study who were aged 50 to 59 years in 1980 and did not report a diagnosis of cancer or AMD at the beginning of the study. Additional women entered the analytic cohort as they reached 50 years of age. <h3>Main Outcome Measure.</h3> —Incidence of AMD with visual loss. <h3>Results.</h3> —During 556 338 person-years of follow-up, 215 women were newly diagnosed as having AMD. After adjusting for other risk factors for AMD, women who currently smoked 25 or more cigarettes per day had a relative risk (RR) of AMD of 2.4 (95% confidence interval [CI], 1.4-4.0) compared with women who never smoked. Past smokers of this amount also had a 2-fold increased risk (RR=2.0; 95% CI, 1.2-3.4) relative to never smokers. Compared with current smokers, little reduction in risk was suggested even after quitting smoking for 15 or more years. Risk of AMD also increased with an increasing number of pack-years smoked (P for trend &lt;.001); among women who smoked for 65 or more pack-years, the risk was 2.4 times the risk of never smokers (95% CI, 1.5-3.8). Analyses of dry and exudative types of AMD and other alternative definitions of AMD revealed similar results. <h3>Conclusions.</h3> —Cigarette smoking is an independent and avoidable risk factor for AMD among women. Because AMD is the most common cause of severe visual impairment among the elderly and treatment is not available or is ineffective for most patients, reducing the risk of this disease is another important reason to avoid smoking.